Xinlei Chen1, Guangping Liu1, Shuxiang Wang1, Haiyang Zhang1, Peng Xue2. 1. Department of Orthopedics, Zibo Central Hospital, Zibo, 255000, Shandong, China. 2. Department of Orthopedics, Zibo Central Hospital, Zibo, 255000, Shandong, China. xp5879@126.com.
Abstract
BACKGROUND: Osteoporosis (OP) is increasingly prevalent with the aging of the world population. It is urgent to identify efficient diagnostic signatures for the clinical application. METHOD: We downloaded the mRNA profile of 90 peripheral blood samples with or without OP from GEO database (Number: GSE152073). Weighted gene co-expression network analysis (WGCNA) was used to reveal the correlation among genes in all samples. GO term and KEGG pathway enrichment analysis was performed via the clusterProfiler R package. STRING database was applied to screen the interaction pairs among proteins. Protein-protein interaction (PPI) network was visualized based on Cytoscape, and the key genes were screened using the cytoHubba plug-in. The diagnostic model based on these key genes was constructed, and 5-fold cross validation method was applied to evaluate its reliability. RESULTS: A gene module consisted of 176 genes predicted to be associated with the occurrence of OP was identified. A total of 16 significantly enriched GO terms and 1 significantly enriched KEGG pathway were obtained based on the 176 genes. The top 50 key genes in the PPI network were identified. Then 22 genes were screened based on stepwise regression analysis from the 50 key genes. Of which, 9 genes were further screened out by multivariate regression analysis with the significant threshold of P value < 0.01. The diagnostic model was established based on the optimal 9 key genes, which efficiently separated the normal samples and OP samples. CONCLUSION: A diagnostic model established based on nine key genes could reliably separate OP patients from healthy subjects, which provided novel lightings on the diagnostic research of OP.
BACKGROUND:Osteoporosis (OP) is increasingly prevalent with the aging of the world population. It is urgent to identify efficient diagnostic signatures for the clinical application. METHOD: We downloaded the mRNA profile of 90 peripheral blood samples with or without OP from GEO database (Number: GSE152073). Weighted gene co-expression network analysis (WGCNA) was used to reveal the correlation among genes in all samples. GO term and KEGG pathway enrichment analysis was performed via the clusterProfiler R package. STRING database was applied to screen the interaction pairs among proteins. Protein-protein interaction (PPI) network was visualized based on Cytoscape, and the key genes were screened using the cytoHubba plug-in. The diagnostic model based on these key genes was constructed, and 5-fold cross validation method was applied to evaluate its reliability. RESULTS: A gene module consisted of 176 genes predicted to be associated with the occurrence of OP was identified. A total of 16 significantly enriched GO terms and 1 significantly enriched KEGG pathway were obtained based on the 176 genes. The top 50 key genes in the PPI network were identified. Then 22 genes were screened based on stepwise regression analysis from the 50 key genes. Of which, 9 genes were further screened out by multivariate regression analysis with the significant threshold of P value < 0.01. The diagnostic model was established based on the optimal 9 key genes, which efficiently separated the normal samples and OP samples. CONCLUSION: A diagnostic model established based on nine key genes could reliably separate OP patients from healthy subjects, which provided novel lightings on the diagnostic research of OP.
Entities:
Keywords:
Logistic regression model; Osteoporosis; PPI network; WGCNA analysis
Authors: Sarita A Y Hartgring; Cynthia R Willis; Johannes W J Bijlsma; Floris P J G Lafeber; Joel A G van Roon Journal: Arthritis Res Ther Date: 2012-06-07 Impact factor: 5.156